As known oxygen has a quenching effect on the molecular luminescence of various chemical compounds. This effect has been exploited for imaging oxygen concentrations (partial pressure) in various body portions of humans and animals. Information about the distribution and concentration of various oxygen partial pressure in various body locales is useful as an indication of tissue health, structure, defects, abnormalities and diseases. For example, in traumatic injury, the primary threat to life is often the loss of blood and resulting hemorrhagic shock. The latter results in hypotension, under perfusion of tissue and the blood flow which does occur is abnormally distributed among and within the tissues. As a result, regions in the tissue become hypoxic or relatively devoid of oxygen, the fasculature becomes leaky, and tissue function is compromised. If the damage is sufficiently severe and/or involves essential organs, surgical repair of the traumatic injury and reinfusion of blood may not be sufficient to sustain life. Treatment of trauma victims during transit to the site where surgical repair will occur is designed to alleviate the loss of blood volume, usually by plasma expanders, in an effort to maintain blood pressure. This is believed to improve oxygen delivery to the tissue and therefor stabilize its condition until surgery can be performed. A reliable method for measuring the oxygen pressure in tissue would be an invaluable asset in the critical period between the occurrence of trauma and completion of surgery. The extent of compromise of oxygen delivery to tissue can be accurately followed, helping in such decisions as to whether intervention is necessary, the choice of treatment modality and evaluation of treatment efficacy.
For examples of oxygen mapping devices, see U.S. Pat. No. 5,593,899, which discloses methods and apparatus for imaging internal body structures of animals. The apparatus and methods disclosed in this application are directed to measuring tissue oxygenation through the skin using oxygen dependent quenching of phosphorescence. In addition, there have been additional patents directed to this technology.
U.K. patent application No. GB 2,132,348A, published Jul. 4, 1984, discloses the use of fluorescent materials to measure levels of oxygen in blood both in vitro and in vivo using a fiber optic probe or catheter.
The prior art has disclosed indwelling devices for use during measurement of various blood parameters. For example, U.S. Pat. No. 3,787,119 discloses a catheter having a microlamp and a photosensitive element and other elements including a cup-like element for use in receiving blood and providing electrical output signals by means of wires extending through the catheter.
U.S. Pat. No. 3,814,081 discloses an optical measuring oxygen saturation in blood, as well as blood pressure.
U.S. Pat. No. 4,200,110 discloses a fiber optic pH probe which includes an ion permeable membrane which encloses a guide containing solid material comprised of a hydrophilic copolymer having a pH sensitive dye attached thereto. The probe functions by optically detecting a change in color of the pH sensitive dye when excited by light. A phenol red dye is employed so that it absorbs light at a particular wavelength, with the amount of light being absorbed varying in dependence upon the pH level.
U.S. Pat. No. 4,476,870 discloses a fiberoptic oxygen partial pressure probe. This probe includes a hydrophobic gas permeable envelope which contains an adsorptive support which contains a fluorescent dye. Use of the probe for measuring partial pressure of gaseous oxygen in the bloodstream is based on the principle of dye fluorescent oxygen quenching. With the probe in place with a bloodstream, fluorescent dye is excited by light having a blue wavelength, thus causing the dye to fluoresce at a green wavelength with the intensity of emitted light decreasing (quenching) with increasing levels of the partial pressure of gaseous oxygen in the bloodstream.
U.S. Pat. No. 5,127,405 discloses a fiber optic probe incorporating a luminescent composition which is used to monitor conditions of a subject. A response light from the fiber optic probe is detected and a frequency domain presentation of the response light is derived. Characteristics of the frequency domain representation are used to derive values for luminescent lifetimes or similar decay parameters and these values in turn are translated into the values of the conditions to be sensed.
Finally, U.S. Pat. No. 4,898,175 discloses an apparatus in which an illuminating light is fed by a device emitted from the tip part of an insertable endoscope. The endoscope is inserted into a body cavity and is radiated onto a part of the body to be observed. This illuminating light, having passed through a living body tissue, is imaged by an imaging device provided outside the body. The imaging device delivers a picture image signal to a signal processing device. The signal processing device processes the signal and outputs a video signal to a display device. This device displays the image observed within the living body. See also U.S. Pat. No. 4,974,850.
In addition to the above technologies, oxygen electrodes have also been designed for transcutaneous oxygen measurements. Oxygen electrodes, in contrast to systems which are based on the oxygen dependent quenching of phosphorescence, utilize substantial amounts of oxygen. The oxygen permeability of the skin is low and oxygen consumption by the electrodes can seriously deplete the oxygen pressure at the surface of the skin, resulting in measured oxygen values which are artificially low and which are strongly dependent upon blood flow in the immediate vicinity of the electrodes. In general an oxygen electrode system must compensate by heating the skin to well above normal values in order to maximally dilate the vessels. In the phosphorescence method, the negligible oxygen consumption by the measuring system will permit the use of only one modest heating, primarily to overcome possible vasoconstriction due to depressed body temperature to assure uniform conditions among subjects. Oxygen electrodes further require calibration before each use. The calibration cannot alter with the time of measurement.
See also for example, U.S. Pat. No. 4,474,850, in which there is described a method and associated apparatus for imaging an oxygen-containing internal body portion of a host animal comprising, inter alia, adding to a body fluid of the host animal a phosphorescent composition (e.g., zinc verdin or a metal porphyrin compound) compatible with the body fluid, and in which the phosphorescence of the composition is quenchable with oxygen in the body portion, irradiating the body portion with a pulse of light at a wavelength and for a time sufficient to effect phosphorescence of the composition to be emitted as light from the body portion, scanning across the body portion to measure the decay of the emitted phosphorescence across the body portion, relating any variations in the decay measured across the body portion to variations in structure of the body portion based on oxygen contained by the body portion, and displaying an image of said body portion.
Further, in U.S. Pat. No. 5,501,225, there is described yet another method and apparatus for imaging internal body structure of humans and animals. By this method and apparatus, light focused through an epifluorescence attachment excites a phosphorescent material within a body portion or tissue, with the light emanating from the phosphorescent material being collected from outside of the tissue. However, this method and apparatus suffers from the drawback of not being convenient for isolating and measuring oxygen partial pressure of specific sections of back/portions of tissue samples.
In U.S. Pat. No. 5,593,899, there is described a non- invasive system for measuring tissue oxygen dependent upon quenching phosphorescence entailing, inter alia, a phosphorescent robe or otherwise oxygen-quenchable compound applied to the surface of a skin portion of a human or animal patient via an oxygen impermeable film placed over the probe and skin portion. This system also includes an optical head overlaying the oxygen impermeable film in which the optical head comprises a means for heating the impermeable film and probe. Also provided is a means for providing an excitation light signal for exciting the probe to permit the probe to emit phosphorescent light, and a photodiode circuit to detect the phosphorescent light emitted by the probe to provide an output signal characteristic of the oxygen partial pressure via oxygen quenching measurement of the skin portion proximate to the reflected phosphorescent signal.
Several other sensor devices are known which are useful for measuring oxygen and pH content in human and animal tissue. For example, U.S. Pat. No. 4,758,814 describes a device which is composed of an elongated flexible optical fiber containing a light sensing or light emitting end, and a light collecting and processing end. The light sensing end, which is adapted to be inserted into a human or animal body, i.e. a blood vessel, is composed of a portion of the optical fiber which is covered with a membrane, and which senses and returns light through the optical fiber to the light collecting and processing end which is, for example, a detector comprising photosensitive equipment such as a photomultiplier.
The membrane is constructed of a hydrophilic porous material containing a pH sensitive dye. Several hydrophobic microspheres are embedded in and carried by the membrane, each of which carries a fluorescent dye quenchable by oxygen. Light is supplied to the proximal end of the optical fiber and conveyed through the fiber to the membrane causing the pH sensitive dye to react, and light is thereafter conveyed back through the fiber with an intensity indicative of blood pH level. The oxygen sensitive dye also is caused to fluoresce, and transmit readable fluorescence via the oxygen quenchable dye which varies with oxygen partial pressure.
This reference thus discloses a fiber optic sensitive probe for sensing both pH and oxygen partial pressure, either simultaneously or in sequence, which is made possible by the employ of the composite membrane. As also described in this reference, the hydrophilic membrane containing the pH sensitive dye and the hydrophobic microspheres contained in the membrane which contain the oxygen quenchable dye, i.e. the two measurement vectors, can be admixed with one another the mixture deployed at the same time in the same probe to obtain their respective measurements.
In U.S. Pat. No. 5,127,405, another version of a fiber optic probe is described in which, inter alia, specialized light collecting and processing equipment is employed at one end of an optic fiber and a probe is employed at the other end for insertion into the body. This is described as an oxygen- permeable transport resin in which is embedded a luminescent composition comprising crystals of an oxygen quenchable phosphorescent material. Response light from the fiber optic probe is processed in the detection equipment by derivation of frequency domain representation, and characteristics of the frequency domain are thereafter employed to derive values for luminescence lifetimes or decay parameters, which are corrected into values of conditions to be monitored.
U.S. Pat. No. 4,752,115 discloses an oxygen sensing device which employs an optical fiber, 250 nm in diameter or small enough for insertion into veins and/or arteries, and in which one end is coated with an oxygen sensitive (oxygen quenchable) fluorescent dye which fluoresces light back, dependant upon regional oxygen partial pressure, to the other end which is adapted to receive the fluorescent light and provide an outlet for the light to go to a signal detector to provide oxygen measurement. The oxygen sensing end is made by dipping an end of the optical fiber into a solution containing an oxygen sensitive fluorescent dye, such as, tris (4,7-diphenyl-1, 10-phenanthroline) Ru(II) perchlorate, a carrier polymer, such as, polyvinyl chloride and a plasticizer dissolved in, for example, THF. The plasticizer is said to be necessary for a fast response and high sensitivity. The oxygen sensing end can also include a gas-permeable sleeve about the optical fiber.
Another fluorometric oxygen sensing device is described in U.S. Pat. No. 5,012,809 which employs a fluorometric sensor constructed with silicone polycarbonate bonded to one or more plastic fiber optic light pipes using polymethylmethacrylate glues.
U.S. Pat. No. 4,476,870 discloses a fiber optic probe for implantation in the human body for gaseous oxygen measurement in the blood stream. The probe employs oxygen quenchable dye fluorescence, and uses two 150 .mu.m strands of a plastic optical fiber which end in a tubular envelope packed with fluorescent light-excitable dye placed on a porous absorptive particulate polymeric support. The tubular envelope is made of a hydrophobic, gas-permeable material.
U.S. Pat. No. 4,200,110 discloses a fiber optic pH probe employing an ion-permeable membrane envelope enclosing the ends of a pair of optical fibers, with a pH sensitive dye indicator composition disposed within the envelope.
U.S. Pat. No. 3,814,081 describes another variant of an optical measuring catheter for measuring the degree of oxygen saturation in blood using an illuminating fiber optical system and a light receiving fiber optical system, both of which are arranged along side of each of other, and both having forward ends adapted to be inserted together into the organ of a living body to detect illumination of from 600 to 750 nm to measure blood oxygen concentration. This method does not rely on oxygen quenchable phosphor/fluorophor compounds, but instead employs direct measurement of light absorption of Hb vs. HbO.sub.2 at specific wave lengths.
In another example, U.S. Pat. No. 3,787,119 describes a multiple photometer device mounted in a catheter, which utilizes at least two associated photosensitive cells to measure physical and chemical characteristics of blood in vivo.
Finally, in co-pending U.S. application Ser. No. 08/767,305, now U.S. Pat. No. 5,830,138, the entire disclosure which is incorporated herein by reference, there is described an improved optical probe for use in measuring blood and tissue oxygen partial pressure and pH (CO.sub.2) measurements. In this method and apparatus, a probe is provided for use in measuring blood and tissue oxygen partial pressure and pH (CO.sub.2) measurements in humans and animals, which comprises a fiber optic means effective for transmitting phosphorescent and/or fluorescent light, an oxygen and/or pH probe means situated at one end of the fiber optic means which comprises a portion of the fiber optic means enclosed by a gas permeable membrane, a reservoir means which compromises a solution of an oxygen-quenchable phosphorescence-emitting compound and/or fluorescent-emitting compound situated between the gas permeable membrane end fiber optic means, and further comprising at the other end of the fiber optic means a phosphorescent and/or fluorescent light detection means to receive light from the fiber optic means, to measure tissue and blood oxygen and/or pH. The device further comprises an excitation light-emitting means to provide light to the phosphorescent and/or fluorescent emitting compounds.
In other embodiments of this invention, the oxygen-quenchable phosphorescence-emitting compound and/or fluorescence-emitting compound (hereinafter "phosphor" and fluorophor" respectively) is dissolved in a solvent having substantially the same refractive index as the fiber optic means, and/or the fiber optic means portion comprising the probe means has at least a portion thereof etched or is otherwise provided with a plurality of grooves or depressions to provide additional angled surfaces to aid in scattering excitation light outward into the phosphor and/or fluorophor-containing medium to the fiber optic means, and thereafter back to the light detection means. In a further embodiment the probe means contains a plurality of grooves or depressions, a portion of which contain an oxygen-quenchable phosphor for oxygen measurement and a portion of which contain a fluorophor for pH (CO.sub.2) measurement.
While the above-described methods and apparatus for imaging oxygen partial pressure in tissue using oxygen-dependent quenching of phosphorescence are capable of generating two- dimensional images of oxygen pressure, three-dimensional information has been unobtainable, or relatively difficult to obtain. Such information would be highly beneficial as a diagnostic tool, and in many cases pivotal in quickly, accurately and precisely diagnosing many heretofore difficult to diagnose maladies.